POS0255 PREDICTORS OF ANTIBODY RESPONSE TO COVID-19 VACCINE IN RITUXIMAB TREATED PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASES. A SWEDISH NATIONWIDE STUDY (COVID19-REUMA)
Authors: M. Frodlund, K. Chatzidionysiou, A. Södergren, E. Klingberg, M. Hansson, E. Pin, S. Olsson, A. Bengtsson, L. Klareskog, M. C. Kapetanovic
Journal: Annals of the Rheumatic Diseases (2022)

Background In line with other reports, our group showed that patients treated with rituximab had significant impaired antibody response compared to patients treated with other biologic and targeted and synthetic disease modifying anti-rheumatic drugs (csDMARD). Objectives To investigate predictors of response to COVID-19 vaccination (2 doses of mRNA vaccines, 2 doses of virus vector vaccines or combinations of these) in patients with inflammatory rheumatic diseases (IRD) treated with rituximab and controls. Methods Antibody levels to three antigens: Spike protein full length, Spike S1 and Nucleocapsid C-terminal fragment (to confirm previous COVID-19 infection) were measured in sera collected before vaccination and 2-12 weeks after the second vaccine using a multiplex bead-based serology assay. The antigen-specific cut-off was defined as the median fluorescence intensity signal plus 6x standard deviations across 12 pre-pandemic controls. A good vaccine response was defined as having antibodies over the cut-off level for both spike antigens. Proportion (%) responders was compared between patients and controls (Chi2 test). Patients with IRD receiving last rituximab treatment within a mean (range) 193 (23-501) days before first vaccination participated. Individuals without IRD served as a control group. Predictors of a good vaccine response were explored using multivariate logistic regression analysis adjusted for age, sex, disease duration, diagnosis (systemic vasculitis/RA/JIA/other), concomitant csDMARD, rituximab dose and prednisolone dose. Hazard ratio (chanse) of a good antibody response in relation to time between the last rituximab treatment and vaccination was studied by Kaplan-Meier survival analysis. Results In total, 145 patients receiving rituximab and 61 controls were inclyded. Of these, 82 received rituximab as monotherapy (67% women; mean age 66 years, mean disease duration 13 years; 33% had RA/JIA and 60% vasculitis) and 63 received rituximab+csDMARD (62% women; mean age 66 years; mean disease duration 17 years; 76% had RA/JIA and 10 % vasculitis). Controls (n=61) were 74% women and mean age 49 years. Compared to controls, rituximab patients had lower antibody levels for both spike proteins (p&lt;0.001). Proportion (%) responders among patients receiving rituximab as monotherapy (40.2%) and rituximab+DMARDs (25.4%) was significantly lower than in controls (98.4%) (p&lt;0.001, Chi2). Higher age, concomitant csDMARD at vaccination and shorter time from last rituximab treatment predicted impaired antibody response (multivariate logistic regression model) (Table 1). Longer time between the last rituximab course and vaccination was associated with better antibody response (Figure 1). Table 1. Predictors of good antibody response to two doses of COVID-19 vaccine defined as antibodies over the cut-off level for both spike antigens B p-value OR 95% CI Age at vaccination (years ) -0.04 0.009 0.96 0.93-0.99 Sex (male/female) -9.55 0.209 0.58 0.24-1.36 csDMARD at vaccination (yes/no) -1.08 0.026 0.34 0.13-0.88 Prednisolone (mg/dag) -0.10 0.103 0.90 0.80-1.02 Rituximab dos (1000 mg vs 500 mg) -0.01 0.370 0.99 0.99-1.00 Time between the last rituximab and vaccination (months ) 0.20 0.001 1.31 1.11-1.55 Diagnosis at vaccination (systemic vasculitis vs others) -0.51 0.315 0.60 0.21-1.64 Figure 1. The chance of good antibody response following two doses of COVID-19 vaccine in relation to time between the last rituximab course and vaccination. Conclusion Patients with IRD getting vaccinated with two doses of COVID19 vaccine during the treatment with rituximab have the ability to develop antibody response although the response is impaired. For each month passed after the last rituximab course, the chance of good antibody response increases with 30%. Younger patients receiving rituximab as monotherapy and vaccinated preferably several months after the last rituximab treatment have the highest chance of achieving a good antibody response. Acknowledgements Unrestricted research grants have been received from Roche and starting grants from The Swedish Rheumatism Association Disclosure of Interests Martina Frodlund: None declared, Katerina Chatzidionysiou Consultant of: consultancy fees from Eli Lilly, AbbVie and Pfizer., Anna Södergren: None declared, Eva Klingberg: None declared, Monika Hansson: None declared, Elisa Pin: None declared, Sophie Olsson: None declared, Anders Bengtsson: None declared, Lars Klareskog Grant/research support from: has eceived research grants from Pfizer, BMS, Affibody, Sonoma Biotherapeutics, Meliha C Kapetanovic Consultant of: have received consultancy fees from Abbvie, Pfizer and GSK, Grant/research support from: have received unrestricted research grants from Roche and Pfizer